ENST00000637267.2:c.-340+83_-340+86dupGGGG

Variant names:

• chr2-144520469-A-ACCCC
• rs1303890891
• ENST00000637267.2:c.-340+83_-340+86dupGGGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000637267.2(ZEB2):​c.-340+83_-340+86dupGGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000086 (0 hom.)
• Consequence: ZEB2 ENST00000637267.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630
• Publications: 0 publications found

Genes affected

ZEB2 (HGNC:14881): (zinc finger E-box binding homeobox 2) The protein encoded by this gene is a member of the Zfh1 family of 2-handed zinc finger/homeodomain proteins. It is located in the nucleus and functions as a DNA-binding transcriptional repressor that interacts with activated SMADs. Mutations in this gene are associated with Hirschsprung disease/Mowat-Wilson syndrome. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jan 2010]

ZEB2-AS1 (HGNC:37149): (ZEB2 antisense RNA 1) This gene produces a spliced long non-coding RNA which is a natural antisense transcript corresponding to the 5' UTR of zinc finger E-box binding homeobox 2 (ZEB2). It is thought that this transcript may be involved in the regulation of ZEB2 expression, and may play a role in the progression of bladder cancer. [provided by RefSeq, Aug 2015]

ENSG00000273537 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000637267.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2-AS1	NR_040248.2		n.284+189_284+192dupCCCC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2	ENST00000637267.2	TSL:5	c.-340+83_-340+86dupGGGG		intron	N/A	ENSP00000490293.2	A0A1X7SC99
	ZEB2-AS1	ENST00000427278.8	TSL:5	n.1010_1013dupCCCC		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000273537	ENST00000621340.1	TSL:6	n.19_22dupCCCC		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.000122 AC: 6 AN: 49370 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000389

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000706

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000864 AC: 17 AN: 196854 Hom.: 0 Cov.: 0 AF XY: 0.000119 AC XY: 13 AN XY: 109052

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000389 AC: 2 AN: 5146

American (AMR) AF: 0.0000865 AC: 1 AN: 11566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4342

East Asian (EAS) AF: 0.00 AC: 0 AN: 8114

South Asian (SAS) AF: 0.00 AC: 0 AN: 39460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 636

European-Non Finnish (NFE) AF: 0.000109 AC: 12 AN: 109856

Other (OTH) AF: 0.000212 AC: 2 AN: 9434

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000121 AC: 6 AN: 49408 Hom.: 0 Cov.: 0 AF XY: 0.0000914 AC XY: 2 AN XY: 21874

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000388 AC: 4 AN: 10304

American (AMR) AF: 0.00 AC: 0 AN: 4102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1666

East Asian (EAS) AF: 0.00 AC: 0 AN: 1034

South Asian (SAS) AF: 0.00 AC: 0 AN: 876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 100

European-Non Finnish (NFE) AF: 0.0000706 AC: 2 AN: 28310

Other (OTH) AF: 0.00 AC: 0 AN: 634

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00169570), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1303890891; hg19: chr2-145278036;